Phagocytosis is the major mechanism for combating staphylococcal
infection. Antibodies are produced which neutralize toxins and promote
opsonization. However, the bacterial capsule and protein A may interfere with
phagocytosis. Biofilm growth on implants is also impervious to phagocytes.
Staphylococci may be difficult to kill after phagocytic engulfment because they
produce carotenoids and catalase which neutralize singlet oxygen and superoxide,
which are primary phagocytic killing mechanisms within the phagolysosome.

Treatment

Hospital acquired infection is often caused by antibiotic resistant
strains (e.g. MRSA) and can only be treated with vancomycin or an
alternative. Until recently, infections acquired outside hospitals have been treated with
penicillinase-resistant ß-lactams. However, many of the community
associated (CA) staphylococcal infections are now methicillin resistant.
Particularly in Georgia, Texas, and California, the prevalence of
CA-MRSA is widespread. Over 60% of abscess isolates from the emergency
department of an Austin, Texas hospital yielded MRSA. These organisms are
uniformly resistant to penicillins and cephalosporins. The infections have been
treated with combination therapy using sulfa drugs and minocycline or rifampin.

Vaccines

No vaccine is generally available that stimulates active immunity
against staphylococcal infections in humans. A vaccine based on fibronectin binding protein
induces protective immunity against mastitis in cattle and might also be used
as a vaccine in humans. However, vaccine therapies
represent a new and innovative approach in broadening the available
clinical tools against the global health problem of community and
healthcare-associated S. aureus bacterial infections.

Hyperimmune serum or monoclonal antibodies directed towards surface
components (e.g., capsular polysaccharide or surface protein adhesions)
could theoretically prevent bacterial adherence and promote
phagocytosis by opsonization of bacterial cells. Also, human hyperimmune serum could
be given to hospital patients before surgery as a form of passive
immunization.

When the precise molecular basis of the interactions between
staphylococcal adhesins and host tissue receptors is known, it might be possible to
design compounds that block the interactions and thus prevent bacterial
colonization. These could be administered systemically or topically.

An experimental bivalent vaccine against Staphylococcus
aureus is reported to be safe and immunogenic for approximately 40
weeks in patients with end-stage renal disease undergoing hemodialysis.
The vaccine called StaphVAX is composed of S. aureus
type 5 and 8 capsular polysaccharides conjugated to nontoxic recombinant Pseudomonas
aeruginosa exotoxin A. In randomized trials, one injection of the
vaccine was administered to 892 hemodialysis patients. Between weeks 3 and 40,
11 cases of S. aureus bacteremia were diagnosed in the
vaccinated group compared with 26 cases in a control group. Nearly 90% of patients
receiving the vaccine generated antibodies to the two capsular
polysaccharides. A decrease in vaccine efficacy after week 40 correlated with a decrease
in S. aureus antibodies. The investigators did not believe that
use of StaphVAX would be limited to hemodialysis patients. For example,
the vaccine might be used in cases where healthy individuals come into
the hospital for elective surgery, such as a joint replacement. Such
patients do not require protection for the rest of their lives; what they need
is protection for a short period while they are in the hospital.

The pharmaceutical company Nabi has developed a trivalent staphylococcal polysaccharide conjugate
vaccine called TriStaph. It contains the two main capsular types, 5 and 8, found
in the outer coating of more than 80% of S. aureus strains, conjugated to nontoxic
recombinant Pseudomonas exotoxin A. To enhance the efficacy of this vaccine, a surface
polysaccharide, 336, is added. S. aureus Type 336 accounts for the approximately 20% of
S. aureus infections that do not form a polysaccharide capsule in the human bloodstream.
The 336 conjugate vaccine, evaluated in a phase I/II human trial, was shown to be safe and to
generate antibodies in humans that are specific and mediate protection against 336-positive
strains of S. aureus. Together, these three polysaccharide conjugates cover all clinically-significant
serological types of S. aureus.

Since toxins are major contributors to the virulence of S. aureus
causing infections in the hospital as well as the community, Nabi
identified two vaccine candidates that cover relevant toxins. One of the toxins in animal models
is produced by almost all clinical isolates and the other is a toxin associated
with severe skin and soft tissue infections caused by the newly emerging
multi-drug resistant community-acquired MRSA strains. Genetic
engineering technology was used to render the toxins nontoxic so they
can be used safely. Adding these two components to Tristaph
produces a multi-targeted S. aureuspolysaccharide
conjugate vaccine and toxoid vaccine called PentaStaph.